We have detected a specific hormone-regulated protein in the human endometrium. Preliminary studies on this protein, which we have designated "Progestin-dependent Endometrial Protein" or PEP, strongly suggest that PEP is a potentially useful marker to monitor uterine responses to endogenous and exogenous progestins in women. The overall aim of this 4-year investigation is to study clinical utility of PEP. The specific aims are i. to establish mean and variance of daily luteal phase serum PEP levels during normal menstrual cycle, ii. to study utility of serum PEP levels in the diagnosis of corpus luteum defects, iii. to establish mean and variance of daily levels and of doubling times of serum PEP and hCG during early pregnancy, iv. to study utility of daily levels or doubling times of serum PEP and hCG as prognosticators of pregnancy outcome, v. to study effects of exogenous progestins on serum PEP levels in hysterectomized and non-hysterectomized premenopausal women, vi. to study utility of determinations of serum or peritoneal fluid PEP, anti PEP and immune complexes in the detection of autoimmune reaction in women with unexplained infertility or in endometriosis patients, vii. to produce monoclonal antibodies against PEP, and, subsequently, viii. to develop simple and sensitive assays of PEP, utilizing monoclonal anti-PEP antibodies for large-scale clinical trials using standardized assay reagents. The proposed study is a collaborative effort by a reproductive biologist, an immunologist, and three clinical reproductive endocrinologists. The project will utilize patient populations from 4 different medical centers. The studies will rely on sensitive and specific RIA procedures, most of which have been either established or being set up in Principal Investigator's laboratory. It is hoped that the results of these studies will lead to the development of laboratory tests with potential applications in i. the diagnosis of corpus luteum or endometrium-related defects in infertility and in abnormal pregnancies, ii. monitoring effects of progestin therapy in threatened pregnancies or in endometrial cancer, iii. monitoring endometrial responses in women exposed to progestin-containing contraceptives, including oral contraceptives, and IUD's. Finally this application is being submitted in response to the announcement No. NICHD/13-864 entitled "Reproductive Disorders in Women".